Aritmil

General characteristics. Structure:

International and chemical names: amiodaron; (2-butylcoumarone-3-silt) [4-[2-dietilamino) etoks] - 3,5-diyodofenit] a metanon a hydrochloride;
main physical and chemical properties: tablets of a round form, white or almost white color, with a flat surface with slanted edges and risky;
structure: 1 tablet contains 200 mg of Amiodaronum of a hydrochloride;
excipients: starch corn, cellulose microcrystallic, calcium stearate, povidone, lactoses monohydrate.

Pharmacological properties:

Pharmacodynamics. Antiarrhytmic means. The mechanism of action is caused by blocking of ion channels of cellular membranes of cardiomyocytes (mainly potassium and in insignificant degree calcic and sodium). Extends duration of action potential and the effective refractory period in all sites of the carrying-out system of heart, including sinus and an AV node and ventricles. Reduces automatism of a sinus node and the ectopic centers, prolongs conductivity in Purkinye's fibers and additional conduction paths at patients with a WPW syndrome (Wolf-Parkinson-Whyte).
Drug shows anti-anginal effect which is caused by its anti-adrenergic action. Drug it is non-competitive blocks a- and b-adrenoceptors. Amiodaronum lowers the peripheric vascular resistance and system arterial pressure a little.

Pharmacokinetics. Drug contains ≅ 37,3% of iodine on weight, has high lipophilicity, after oral administration drug is soaked up slowly and not completely (20–55% of the accepted dose). After a single dose the maximum concentration in blood is established in 3–7 hours; has the large and variable volume of distribution as result of intensive accumulation in a fatty tissue and bodies with intensive blood circulation and blood supply (a liver, lungs, a spleen). Communication with proteins of a blood plasma makes 96%, and 10–50% of drug get through a placental barrier; ¼ part of the entered dose gets into breast milk. It is intensively metabolized in a liver with formation of an active metabolite – a dezetilamiodarona. The main way of removal – with bile. The elimination half-life (T _1/2) drug makes at long therapy – 53±24 days. The t _1/2 dezetilamiodaron equals on average to 61 day. After the treatment termination the therapeutic level of Amiodaronum in plasma remains within nine months. It is not removed at a hemodialysis.

Indications to use:

Prevention and treatment of paroxysmal disturbances of a cordial rhythm: sinus tachycardia, supraventricular tachyarrhythmia, including trembling and atrial fibrillation, ventricular tachyarrhythmia, ventricular and supraventricular premature ventricular contraction; disturbance of a rhythm at patients with a WPW syndrome; prevention of attacks of stenocardia (stable, unstable, spontaneous) at patients with disturbance of a cordial rhythm at whom treatment by other antiarrhythmic drugs was ineffective or it is contraindicated. 

Route of administration and doses:

1. Use inside at life-threatening arrhythmias:
1.1) the daily medical dose makes 800–1600 mg (better to divide into 2–4 receptions within a day and to appoint together with food, especially at a dose more than 1000 mg, and for patients with gastrointestinal disturbances) during 1–3 weeks or longer;
1.2) after achievement of therapeutic effect to lower a daily dose to 400–800 mg (in 2 receptions) during about 1-3 weeks, and then to turn to the supporting daily dose — 400 mg (into 1–2 receptions) and even 200 mg of 1 times a day during a necessary course of treatment.
2. Intake at various arrhythmias:
2.1) Bouveret's supraventricular disease: the medical dose makes 600 mg/days within 8–15 days; maintenance dose of 100-200 mg/days;
2.2) paroxysmal blinkings and atrial flutters: the medical dose makes 600–800 mg/days within 15–30 days (sometimes to 1000 mg/days); a maintenance dose of 300-400 mg/days with gradual decrease by 200 mg/days every 15-30 days;
2.3) potentially dangerous ventricular arrhythmias (frequent, pair ventricular premature ventricular contraction, repeated episodes of ventricular tachycardia): the medical dose makes from 600–800 mg/days; a maintenance dose – 300–600 mg/days;
2.4) frequent paroxysms of ventricular tachycardia or repeated episodes of fibrillation of ventricles: the average medical dose makes 1000 mg/days within 15–30 days, the maximum daily dose _(sutmax) in some cases — to 2000 mg within 7–10 days; an average maintenance dose — 700 mg/days (from 600 to 800 mg/days);
2.5) arrhythmias at children: it is necessary to consider that at children the therapeutic effect of drug occurs quicker, and duration of action is less, than at adults. The initial daily dose for children on average makes 10 mg/kg within 10 days or before achievement of therapeutic effect. After achievement of desirable results the daily dose is reduced to 5 mg/kg. The supporting daily dose makes 2,5 mg/kg.

Features of use:

With care appoint drug to patients of advanced age as the risk of development of side toxic effects increases. Before an initiation of treatment each patient needs to carry out an ECG, to determine the TTG level and potassium in a blood plasma. It is necessary to consider that the frequency of emergence and weight of side effects of drug are dozozavisyashchy. At Aritmil's appointment can be required by patients with heart failure simultaneous use of cardiotonic means. During treatment by drug, and also when developing new arrhythmias or exacerbations of a disease it is necessary to spend ECG monitoring each 3 months. Prolonged treatment in high doses can lead to changes of indicators of an ECG: increase in intervals of R-R, Q-t, expansion of the QRS complex, reduction of amplitude of a tooth of T, emergence of a U-wave. Aritmil with extra care appoint the patient with congestive heart failure in view of risk of deterioration in hemodynamic indicators, and also at AV blockade of the I degree. The patient should be informed that in case of development of side effects (including at ChSS will make less than 55 blows/min.) it is necessary to stop treatment and to report immediately about it to the doctor. At development of symptoms hypo - or a hyperthyroidism it is necessary to cancel drug. At patients with an abnormal liver function Aritmil appoint in lower doses.
During treatment by Aritmil obligatory regular monitoring of the following functions and indicators is necessary: auscultation of lungs in view of risk of development of a pneumopathy (if necessary carry out roentgenoscopy or a X-ray analysis of bodies of a thorax); periodic control of indicators of function of external respiration; ophthalmologic inspection prior to treatment and periodic survey during treatment; control of function of a thyroid gland at prolonged treatment. It is necessary to observe extra care when performing surgeries using an anesthesia in view of risk of emergence of cardiodepressive, hypotensive and aritmogenny effect of Aritmil at a combination to anesthetics. At prolonged treatment by drug it is necessary to avoid insolation that is caused by probability of development of sunblisters. Aritmil is contraindicated at pregnancy. About 25% of the dose accepted by mother are found in breast milk therefore Aritmil do not appoint during feeding a breast.

Side effects:

Side effects at treatment by Aritmil depend on a dose and duration of therapy:
from cardiovascular system: bradycardia (degree depends on a dose) often has an asymptomatic current, however can be followed by clinical symptomatology, are possible sinuatrial or AV-blockade. Pro-arhythmic effects of Aritmil, development and deterioration in a course of the existing arrhythmias can be a cause of infringement of function of a thyroid gland, including in connection with administration of drug; development/aggravations / symptoms of heart failure;
from the alimentary system: anorexia, nausea, vomiting, locks, metal smack in a mouth;
from vegetative and TsNS: paresthesia, a tremor, a headache, feeling of fatigue, a myopathy, retrobulbar neuritis, in single cases – benign intracranial hypertensia, dreadful dreams, auditory hallucinations; unusual weakness in muscles of extremities; the ataxy – the most frequent side effect which can arise after the beginning of therapy after a while and keeps long time (do1 years) after cancellation.   
from respiratory system: alveolar intersticial pneumonia,  fibrosis,  pleurisy, bronchitis, pneumonia (with a lethal outcome), a bronchospasm (especially at patients with heavy respiratory insufficiency or bronchial asthma); clinical manifestations of the specified morbid conditions: short wind, cough;
from organs of sight: adjournment of lipofuscin in a cornea epithelium; complaints to emergence of color auras or illegibility of contours; seldom neuropathy or optic neuritis;
from endocrine system: at prolonged use emergence of a hypothyroidism is possible, is more rare – a hyperthyroidism;
dermatological reactions: a photosensitization, a lead-blue or bluish xanthopathy, rash on skin, occasionally — an allopecia, allergic reactions;
others: sometimes vasculitis, renal failure, thrombocytopenia, hemolitic or aplastic anemia. 

Interaction with other medicines:

Due to the long elimination from an organism Aritmil can interact with other medicines in several weeks and even months after its cancellation! Simultaneous use of Aritmil with anesthetics can strengthen hypotensive effect and cause bradycardia, resistant to treatment by atropine. Joint reception with other antiarrhytmic drugs (quinidine, procaineamide, флекаинид, Phenytoinum Disopyramidum, Procainum) strengthens therapeutic effect, however at the same time the risk of development of proaritmogenny action increases. Simultaneous use with quinidine, Disopyramidum, procaineamide or meksiletiny can cause significant increase in an interval of Q-t. So at urgent combined use of Aritmil with antiarrhytmic means of the I class the dose of these drugs needs to be lowered by 30–50% with a gradual exception them from the scheme of treatment. Aritmil exponentiates effect of anticoagulants (warfarin, neodicoumarin): the effect is celebrated for 4–6 day after an initiation of treatment by drug and proceeds within several weeks or even months after its cancellation. In such cases it is reasonable to lower a dose of anticoagulants on 1/3–1/2 on condition of regular control of indicators of a prothrombin ratio. Aritmil's combination with β-adrenoblockers and antagonists of calcium ions leads to development of bradycardia, AV blockade, hypotension. Drug increases concentration of digoxin in blood serum to toxic values in this connection the dose of cardiac glycoside needs to be lowered to 50% of therapeutic and to carry out further obligatory monitoring of its concentration to blood. Simultaneous use with saluretics, glucocorticosteroids increases risk of development of the arrhythmia caused by decrease in level of potassium ions. Holestiramin reduces T _1/2 and Aritmil's level in plasma, Cimetidinum, on the contrary, increases. Simultaneous use with medicines for which the photosensitizing effect is inherent can lead to increase in expressiveness of a photosensitization. Drugs of iodine increase Aritmil's concentration in blood and symptomatology of yodozavisimy complications.

Contraindications:

Weakness of a sinus node, sinus bradycardia, atrioventricular blocks of II and III degrees; the patient with fraction of emission less than 0,40 (big risk of sudden death) and with previously revealed dysfunction of a thyroid gland (hypo - or a hyperthyroidism), hypersensitivity; hypopotassemia, pregnancy, lactation. Hypersensitivity to compound drug. 

Overdose:

Arterial hypotension, sinus bradycardia, development of a sinuatrial or atrioventricular block of II and even III degree.
Treatment: there is no specific antidote. On condition of recent administration of drug it is inside reasonable to cause vomiting and to provide a gastric lavage. In case of bradycardia appoint atropine or β1-адреномиметики (Dobutaminum), if necessary pacemakers use. At hypotension drugs with cardiotonic action or hypertensive drugs can be used. Aritmil and his metabolites are not allocated at dialysis.

Storage conditions:

To store in the unavailable to children, dry, protected from light place at a temperature not above 25 °C. A period of validity – 4 years.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging. On 2 planimetric packagings in a pack.